Sketchy Pharm Notes Pdf

[Valorie Carlee]

Youmust download these decks to your computer, NOT to your phone. You must also have Anki installed on your computer. *The file you will download is a zip file (a compressed file), thus, you will have to open these zip files to see the Anki decks.* Once you download them your computer that has Anki installed, open them. They will open directly into your Anki app. Now that they are on your computer, you can sync your Anki account with your phone so that you can access them on the go.

Hi! I used your micro deck and i found it incredibly useful! Now that i am trying to download the pharm deck, it says the decks arent available anymore :/ Are you going to re-upload them? Thanks again!

Thank you so much for putting your work into these decks! It was recommended to me by another M2 and it has been fire in terms of retention. Using your decks with the printed Sketchy Medical Notes PDF for focused visual associations.

For example, if I watched the benzodiazepine sketchy video and only wanted to do the anki cards associated with that video, would there be a way for me to easily find and just review those cards? Thanks for the quick reply!

Ah, I get your question now! Haha. If you have downloaded the deck, you will see that the cards are separated by subject. The folders are separated into cardio/renal, antimicrobials, antineoplastics, autonomic drugs, GI/endocrine, neuro/psych, etc. So you can study those folders selectively, but not by specific video. That being said, you can easily edit the deck to your pleasing. You if you wanted to add tags, you could do that for yourself ?

Yes! You can download them via the link in this post ? it will take you to a google drive. Are you having issues? If so, first try downloading to your computer with the Anki application downloaded already. Then, you can sync your Anki account to your phone.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Atherosclerosis is a major cause of acute coronary syndrome and stroke. Foam cell formation in macrophages is involved in controlling plaque stability and the pathogenesis of atherosclerosis. Accordingly, many studies have examined the processes of lipid incorporation, such as scavenger receptor-mediated uptake of oxidized low-density lipoprotein, in cells. In addition to receptor-mediated machinery, growing evidence has suggested that pinocytosis, which is a receptor-independent endocytic pathway, is associated with foam cell formation when a sufficient number of lipoproteins is accumulated around cells. Pinocytotic engulfment of nanoparticles is initiated by plasma membrane ruffling in a phosphatidylinositol-3 kinase-dependent manner. Subsequent to pinosome closure, the majority of pinosomes are internalized through endocytic processes, and they can be recycled into the plasma membrane. These pinocytotic processes are modulated by small GTPases and their cytoskeletal rearrangement. Moreover, pinocytotic abilities may vary between immunological subsets in cells. Accordingly, macrophages may show diverse pinocytotic abilities depending on the surrounding microenvironment. This review summarizes the current understanding of pinocytotic engulfment of lipoprotein in macrophages, and discusses how this endocytic process is governed under hypercholesterolemic conditions.

Ischemic heart disease is the leading cause of death globally. Atherosclerosis is a major risk factor for coronary disease because expansion of such eccentric thickening of the arterial wall can lead to thromboembolism and thrombotic occlusion. Numerous basic and epidemiological studies have shown that an abnormality of cholesterol handling, excessive adaptive response to vascular insults, and inflammation burden are associated with the pathogenesis of atherosclerosis (1, 2). Among these events, cholesterol accumulation in macrophages is an essential process to expand atherosclerotic plaques and is a major factor for defining plaque stability (3, 4). Several endocytic pathways for internalizing low-density lipoprotein (LDL) cholesterol have been reported. Scavenger receptors, such as scavenger receptor-A, CD36, and lectin-like oxidized LDL receptor 1 (5, 6), in macrophages recognize oxidized LDL, but not native LDL, to internalize LDL through the conventional endocytic process. In addition to the receptor-mediated pathways, macrophages enable the incorporation of nanoparticles through pinocytosis. Pinocytosis is a fundamental cellular process that engulfs extracellular fluids. Pinocytosis is categorized into micropinocytosis and macropinocytosis, which are endocytic processes that engulf small particles (typically 0.2 μm), respectively (7). Such pinocytotic engulfment in macrophages, which occurs spontaneously and can be further modified by environmental factors, are related to the innate immune system to monitor surrounding antigens and microbial-associated molecules. Growing evidence has suggested that pinocytosis is mediated through incorporation of native LDL, thereby inducing formation of foamy macrophages (8). This mini review summarizes the recent understanding of internalization and trafficking of pinosomes and their regulatory mechanisms.

The pinocytotic deposition of native LDL is sufficient to convert cultured macrophages into foam cells (9). Pinocytotic uptake is independent of the degree of LDL oxidation and does not saturate (7), and the molecular mechanisms underlying pinocytotic LDL uptake are distinct from those of receptor-mediated pathways. Indeed, targeted deletion of the macrophage scavenger receptors scavenger receptor-A and CD36 does not inhibit pinocytotic LDL uptake in macrophage-colony stimulating factor (M-CSF)-differentiated macrophages (10). Generally, macropinocytotic internalization of nanoparticles is divided into plasma membrane ruffling and pinosome closure, which are regulated by submembranous actin organization. Small GTPases have central roles in this cytoskeletal regulation. Ras-GTP drives the activation of phosphoinositide 3-kinases (PI3Ks), which generates patches of PtdIns(3,4,5)P3 (11). The Rho family GTPase Rac and actin-nucleation-promoting factors, such as SCAR/WAVE complex, enable binding to these patches, which nucleates actin filaments. In addition to actin-regulating factors, phospholipase Cγ can be activated by PtdIns(3,4,5)P3, thereby generating diacylglycerol and subsequent activation of protein kinase C, which is involved in the positive regulation of pinocytosis (12). Kruth and colleagues investigated mechanisms underlying pinocytosis using pharmacological approaches in M-CSF-differentiated macrophages, and found that pinocytosis was inhibited by a broad-range PI3K inhibitors (10). In contrast, inhibition of the class I PI3K isoforms β, γ, or δ did not affect micropinocytosis in M-CSF-stimulated macrophages. Similarly, macrophages from mice expressing dominant-negative class I PI3K β, γ, or δ isoforms had no inhibitory effects. Therefore, PI3Ks, excluding class I isoforms, drive macropinocytosis in macrophages. Pharmacological screening of signaling pathways has shown that dynamin, microtubules, actin, and vacuolar type H(+)-ATPase appear to be associated with pinocytotic uptake (10). Accordingly, phosphoinositide metabolism accompanied by cytoskeletal regulation are indispensable even for pinocytotic LDL uptake in macrophages (Figure 1).

Overview of pinocytotic deposition of low-density lipoprotein cholesterol in macrophages. Phosphoinositide 3-kinase drives pinocytotic plasma membrane ruffling. Small GTPases are associated with trafficking and recycling of pinosomes, as well as with pinocytotic plasma membrane regulation, and have diverse actions in pinocytotic low-density lipoprotein cholesterol uptake in macrophages. While pinocytosis appears to be optimized in an alternative (M2) macrophage subset, certain elements, such as Toll-like receptor 4 (TLR4)-mediated signaling, enable the restoration of pinocytosis, even in an inflammatory (M1) subset. TLR4 driver lipopolysaccharide (LPS) can polarize macrophage differentiation toward M1 subset, and activates pinocytotic activation through unknown mechanisms. Chemokine (C-C motif) ligand 19 reportedly possesses similar pinocytotic effects in the cells. In the case of mmLDL-differentiated macrophages, cytoskeletal rearrangement appears to be driven through TLR4/Ras/Raf/ERK/MEK axis independently of PI3K signaling. Furthermore, pro-inflammatory cytokine TNF-α upregulates calpain-6, a non-proteolytic isoform of calpain protease family, to inhibit CWC22-mediated Rac1 splicing. This interferes with endosomal recycling pathway, and in turn increases lysosomal processing of endosome-derived lipoprotein cholesterol to generate cytosolic lipid droplets. In contrast to M1 subset, macrophage-colony stimulating factor (M-CSF)-differentiated M2 macrophages exhibits phosphatidylinositol 3-kinase (PI3K)-dependent cytoskeletal rearrangement and membrane ruffling. Similarly, thrombospndin-1 enables to elicit CD47-mediated activation of PI3K and subsequent pinocytotic uptake of native LDL. In this case, it is likely that Akt3 negatively regulates Cdc42 and acyl-CoA cholesterol acyltransferase 1 to decelerate pinocytotic cholesterol deposition in the cells. ACAT1, acyl-CoA cholesterol acyltransferase 1; CCL19, Chemokine (C-C motif) ligand 19; EE, early endosome; LE, late endosome; LPS, lipopolysaccharide; M-CSF, macrophage-colony stimulating factor; mmLDL, minimally modified low density lipoprotein; PI3K, phosphatidylinositol 3-kinase; PIP3, phosphatidyl inositol 3-phosphate; Rac1, Rac family small GTPase 1; RE, recycling endosome; TLR4, Toll-like receptor 4; TNF-α, tumor necrosis factor-α; TSP-1, thrombospndin-1.

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